Protein therapeutics are the fastest-growing class of US Food and Drug Administration (FDA)-approved drugs to treat the most difficult-to-manage human diseases, such as cancer, diabetes, and cardiovascular and neurologic disorders. However, the current regimen is mainly restricted to extracellular targets, due to the inability of proteins to enter cells. Exosomes, natural nanovesicles circulating in the human body, possess intrinsic ability to deliver various protein cargoes into recipient cells, thus representing an untapped source of effective delivery carrier toward intracellular targets.
Exosomes are lipid bilayer-enclosed extracellular vesicles that transport proteins, nucleic acids, and lipids between cells. In mammals, exosomes are actively released by almost all types of cells, exist in body fluids, and circulate in the blood. Exosomes are recognized and endocytosed by tissue cells via specific interactions between surface-membrane proteins, where after they deliver their molecular cargo. Therefore, they function in cell-cell communication and play important roles in immunodefense, pathogen spread, inflammation, tumor metastasis, and tissue repair. Exosomes are designed by nature to deliver a large and specific cargo of functional biomolecules, a feature that is guiding the development of exosome-based vehicles for targeted delivery of therapeutic agents. These studies, however, are impacted by gaps in our knowledge of exosome biogenesis and in approaches to engineer exosomes with a molecular cargo that enhances their uptake by target cells. The present invention advances the art by providing engineered exosomes for the delivery of bioactive cargo using transmembrane vesicular stomatitis virus glycoprotein (VSVG).